Gis1 is required for transcriptional reprogramming of carbon metabolism and the stress response during transition into stationary phase in yeast.

Transition from growth to the stationary phase in yeast is still poorly understood. Previously, we identified a group of yeast genes that are universally upregulated upon starvation for different macronutrients. Here, we demonstrate that the Gis1 transcription factor and the Rim15 kinase are responsible for the upregulation of many of these genes. In chemostat cultures, gis1 or rim15 mutant cells are outcompeted by their wild-type parents under conditions resembling the later stages of diauxie (glucose-limiting) and post-diauxie (ethanol as a carbon source). Whilst Gis1p and Rim15p have distinct functions in gene repression, the growth defects of gis1 or rim15 deletants can be accounted for by the overlapping functions of their protein products in promoting the expression of genes involved in glutamate biosynthesis, the glyoxylate cycle, the pentose phosphate pathway and the stress response. Further, we show that the sets of GIS1- and RIM15-dependent genes and the degree of their regulation change in response to the identity of the carbon source, suggesting the likely dynamics of gene regulation exerted by Rim15p and Gis1p during different phases of the transition into stationary phase. In particular, Rim15p is required for the expression of genes involved in gluconeogenesis/glycolysis and glycerol biosynthesis only when ethanol is used as the carbon source. In agreement with this, Rim15p is shown to act in parallel with Hog1p to defend cells against osmotic stress.